Expert Review of Anti-infective Therapy

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/ierz20

Low pH Hypromellose (Taffix) nasal powder spray

could reduce SARS-CoV-2 infection rate post mass-
gathering event at a highly endemic community:
an observational prospective open label user
survey

Klang Shmuel, Megiddo Dalia, Lapidot Tair & Naparstek Yaakov

To cite this article: Klang Shmuel, Megiddo Dalia, Lapidot Tair & Naparstek Yaakov (2021)
Low pH Hypromellose (Taffix) nasal powder spray could reduce SARS-CoV-2 infection rate
post mass-gathering event at a highly endemic community: an observational prospective
open label user survey, Expert Review of Anti-infective Therapy, 19:10, 1325-1330, DOI:
10.1080/14787210.2021.1908127

To link to this article: https://doi.org/10.1080/14787210.2021.1908127

© 2021 The Author(s). Published by Informa Published online: 01 Apr 2021.

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EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
2021, VOL. 19, NO. 10, 1325–1330
https://doi.org/10.1080/14787210.2021.1908127

ORIGINAL RESEARCH

Low pH Hypromellose (Taffix) nasal powder spray could reduce SARS-CoV-2

infection rate post mass-gathering event at a highly endemic community: an
observational prospective open label user survey
Klang Shmuela, Megiddo Daliab*, Lapidot Tairb and Naparstek Yaakovc
a
Faculty of Social Welfare & Health Sciences, School of Public Health Israel, University of Haifa, Haifa, Israel; bclinical development, Nasus Pharma,
Tel Aviv, Israel; cHadassah Medical Center, Jerusalem Israel, and the Scientific Director of Meuhedet HMO Research Institute, Jerusalem, Israel

ABSTRACT ARTICLE HISTORY

Objectives: Bney Brak city tops Israel’s COVID-19 infection rate and mortality. Before the Jewish New Received 5 February 2021
Year (two-day gathering) SARS-CoV-2 PCR positivity rates were 17.6% and reached 28.1% two weeks Accepted 18 March 2021
later Taffix – an innovative nasal powder creates a protective gel over the nasal mucosa blocking viruses KEYWORDS
from infecting nasal cells, was tested for efficacy in preventing SARS CoV2 infection. SARS-CoV-2; prevention;
Methods: In a prospective users survey, 243 members of an ultra-orthodox community that partici­ Hypromellose; nasal spray;
pated in two days prayers were followed for 14 days following this ‘superspread’ event. Eighty-three low pH
used Taffix throughout holiday’s prayers and the following two weeks (ITT). Eighty-one used it regularly
(PP). Two used it rarely if at all. The remaining 160 did not use Taffix.
Results: After 14 days, 0/81 (0%) of (PP) Tafffix users, 2/83 (2.4%) of (ITT) Taffix users and 16/160 (10%)
nonusers were infected. Odds ratio for infection among Taffix users was 0.22, a reduction of 78% (95%CI
1%–95%). No side effects reported.
Conclusion: Taffix could be an additional tool against COVID19 spread, in addition to recommended
safety measures. This is the first time that a prevention measure of SARS-CoV-2, beyond the use of
masks, has proved effective.

1. Introduction ingredient – Hydroxypropyl methyl cellulose, (Hypromellose

or HPMC) is a muco-adhesive gel-forming cellulose derivative.
On September 18, 2020, Israel was a world leader in the
Upon reaching the nasal mucosa HPMC is known to absorb
number of new COVID-19 cases per million citizens. The infec­
fluids and create a micron-sized gel [4] . The gel covers the
tion rate among its ultra-orthodox communities was double
nasal cells and prevents viruses from engaging with the recep­
that of the general population. In the city of Bney Brak (popu­
tors that are necessary for the viral penetration into the cells.
lation ~200000, mostly ultra-orthodox jews) on
Additionally, Taffix creates a local acidic microenvironment of
September 30th there were 23.6 confirmed COVID-19 patients
pH 3.5 on mucosal surfaces, which remains stable for up to
per 1000 citizens, and a total of 4741 active confirmed cases
5 h. An acidic microenvironment in the nose was shown to
[1]. Of note, the mortality rate in Israel was 182 per million
prevent multiple respiratory viruses such as N1H1 influenza
citizens while the calculated mortality in Bney Brak is more
and Rhinoviruses and recently SARS-C0V-2 from infecting
than double that: 380 per million.
cells [5,6].
In 2020, the New Year holiday (Rosh Hashana) began on
Taffix has been tested in three in vitro studies to gauge its
the evening of September 18 and lasted for two days spent in
effectivity in blocking and disabling respiratory viruses SARS-
closed quarter synagauges ending in large celebrations invol­
CoV-2 and H1N1 influenza and Lentivirus.
ving big crowds. This event raised concern for a potential
The purpose of the study of the SARS-CoV-2 study was to
post-mass gathering outbreak.
test whether the Taffix can form a protective barrier against
The objective of this study was to test the efficacy of Taffix
this virus. Using qRT-SARS-CoV-2 PCR techniques and plaque
nasal spray in preventing the potential after effects of a super
essay Taffix™ treatment reduced the amount of viral RNA by
spreader event caused by mass-gathering ahead of the Jewish
more than 4 logs [6]
New Year.
The purpose of the H1N1 study was to test the direct effect
Indeed, in mid-September just before Rosh Hashana
of the pH of different Taffix formulations on H1N1 virus’ ability
(Jewish New Year) there were about 17.6% positivity rates in
to reduce the viability of MDCK cells. MDCK cells were treated
the city of Bney Brak, and those actually climbed to 28.1% two
with saline, Hypromellose, or Taffix with or without virus.
weeks later [1] A similar trend was identified in other ultra-
H1N1 virus pretreated with saline for 5 minutes reduced cell
orthodox communities both in Israel and in greater NYC [2].
viability to 27%. Pretreatment of viruses with Hypromellose
Viral entry through the nasal mucosa is considered a main
alone (pH-6.8) reduced cell viability to 37% while pretreatment
mechanism in SARS-CoV-2 infection [3]. .Taffix’s main

*
CONTACT Megiddo Dalia dalia@nasusphama.com Nasus Pharma, 29 Harakevet St, Tel Aviv 6618306, Israel
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/),
which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
1326 K. SHMUEL ET AL.
of viruses with Taffix (low pH) for 5 minutes resulted in 88%
cell viability, attesting to ability of Taffix to disable aggressive
respiratory viruses. Another study performed with Lentivirus
containing a green fluorescent reporter which was used as
a model virus, showed a significant reduction in cell infectivity.
(supplementary information 1and 2)
Taffix – is an acidified Hypromellose nasal powder spray
inhaler approved for sale and used for prevention of respira­
tory viral infections. Taffix received CE marketing approval
(DE/CA09/0760/N18/001) and the Israeli Ministry of Health
marketing authorization (Amar- 33010001) and other coun­
tries. Taffix is sold in Israel since early July 2020 and in over
15 countries in Europe and South America reaching hundreds
of thousands of users. No reports of adverse events were
registered in the post-marketing database kept in compliance
with regulatory requirements.
To assess real-life effect of Taffix in reducing SARS-CoV-2
infection rates following an anticipated mass social gathering
in closed environment during the Rosh Hashana holiday, we
conducted a prospective user survey at an ultra-orthodox
synagogue in Bney Brak, a highly endemic community.
2. Materials and methods
This is a prospective user survey of a commercially available
product. Taffix (a powder nasal spray comprised HPMC, citric
acid, sodium citrate, benzalkonium chrloride and menthol
manufactured by Nasus Pharma. Israel) .
We collaborated with a medium-sized synagogue commu­
nity consisting of some 250 members. Based on a pre-
prepared survey procedure all members of the community
received a preliminary notification inviting them to participate
in the survey. . Critical to the cooperation of the community
members and their individual compliance, was the strong
support and encouragement of the spiritual leadership of
the community: the Rabbi and the wardens (Gabbaim).
Typically, in ultra-orthodox communities – this community is
very close knit and its members are well familiar with each
other as well as to well known to the leaders of the commu­
nity. The synagogue serves as the center around which the
community day lives revolves. Importantly, it was clarified to
the volunteers that Taffix offers an extra layer of protection
and does not replace the mandatory use of masks. This was
clearly and repeatedly explained to all participants. Though
a user survey of a commercially available product does not
require Ethics committee approval all participant signed an
informed consent. (supplementary information 3)
Of note: At this synagogue members could not enter or
remain indoors without properly wearing a mask throughout
the whole of the services. The prayer room was divided to
‘capsules’ and every effort was made to prevent mingling of
people beyond their allocated capsule.
Members of the community who expressed their interest in
using Taffix throughout Rosh Hashana prayers and the follow­
ing two weeks were eligible to collect a Taffix bottle at the
synagogue the day before Rosh Hashana prayer and received
written instruction on the proper usage of the device. Family
members residing in the same house hold were also eligible to
receive Taffix bottles (one each). The volunteers committed to
use Taffix whenever encountering a large social interaction
and reapply it every five hours whenever they were leaving
their residence for the following two weeks. Weekly reminders
to all participants were sent directly through the community
e-mail system and close attention and monitoring was carried
out to substantiate the number of confirmed (SARS-CoV-2 PCR
tests offered freely in the city) new cases in the community
All participants declared at the beginning of the study that
they have not contracted COVID before.
SARS-CoV-2 PCR testing (free in Israel) was performed
based on clinical symptoms or in cases of a contact with
a verified COVID case, and in all house hold members of
a verified COVID case.
By the 14 day after the Rosh Hashana holiday the wardens
of the synagogue followed up each family with a personal
phone interview. Members and their families were asked to
report whether they have used Taffix, how often and under
what circumstances they used it, and whether there were new
cases of COVID-19 infection since Rosh Hashana confirmed by
SARS-CoV-2 PCR testing and whether there were any adverse
events while using Taffix. All information from the phone
interview was recorded and summarized. Information about
the total number of confirmed new COVID-19 cases in the rest
of the community was also collected and confirmed.
Confirmed cases were defined as all SARS-CoV-2 PCR positive
cases during days 1–14 of the follow up period. Classification
of a positive case was based only on positive SARS-CoV-2 PCR
test across the two groups of users and non-users. At that time
period serological testing was not available freely and was not
performed.
3. Statistical methods
The analysis of the results was performed first on the ITT
(Intent-to-treat) population data (All members who used
Taffix) and then on the PP (Per-Protocol) population. (mem­
bers who used Taffix regularly according to instruction)
The Fisher’s exact test for the comparison of two propor­
tions (from independent samples), expressed as a percentage,
was applied to compare the contagion rate between Taffix
users and none users.
Fisher’s exact test is used to calculate an exact P-value for
a 2 × 2 frequency table with small number of expected
frequencies.
All tests are two-tailed, and a p-value of 5% or less is
considered statistically significant.
The data were analyzed using the SAS ® version 9.4 (SAS
Institute, Cary North Carolina).
4. Results
Overall, 243 members of the Synagogue participated in the
two days holidays prayers (at least seven hours spent in the
synagogue each day in a closed room). The day before Rosh
HaShana 113 Taffix bottles were collected. Of the 243 mem­
bers, 83 (34%), men women and children above the age of
12 years, (as per Taffix indication) reported Taffix use, of which
81 (98%) reported per protocol use instructed before entering
a populated area and every 5 hours. Two (2%) members used

Taffix ‘once or twice’ throughout the 14 days period160 (66%)
members of the community from this population of families,
either did not collect the Taffix at all or collected it and did not
use it at all, not even once.
The ITT group (83 users) comprised of 29 (35%) females and
54 males (65%), and the non users group of 82 (51%) females
and 78 (49%) males. The two out of 83 ITT group who did not
use Taffix as instructed were males (out of protocol).
28 users (33.7%) were below age 18 though as per Taffix
instruction for use only children above age 12 could use Taffix.
In the non-users group 46.9% were below age 18. 66.3% of the
users were adults (18–40y: 44.6%, 40–60y-18.1% and 3%
above 60) and 53.1% in the non users group. Of 243 members
of the community, eighteen (7%) were confirmed as new
SARS-CoV-2 infections during the 14 days following Rosh
Hashana based on positive SARS-CoV-2 PCR test: Among the
eighteen new confirmed cases sixteen (89%) of them did not
collect or used Taffix, two (11%) collected Taffix but did not
adhere to recommended use, that being only once or twice
throughout the whole two weeks period. One of them was
diagnosed 2 days after Rosh Hashana (possibly exposed prior
to the beginning of the survey). All 81 members who used
Taffix regularly according to the instruction for use were not
infected at all during the study period of 14 days following
Rosh Hashana.
In the ITT population, 2/83 (2.4%) of Taffix users and 16/160
(10%) of Taffix non-users were infected. The odds ratio for
SARS-CoV-2 infection in Taffix users were 0.22 (0.05–0.99,
Mid P exact = 0.028) and therefore a reduction of 78% (95%
CI 1%-95%) in odds of infection.
In the PP population, 0/81 (0%) of the Taffix users and 16/
160 (10%) of the Taffix non-users were infected. The odds ratio
for SARS-CoV-2 infection in Taffix users were 0 (0.00–0.38, Mid
P exact <0.001). (See Figure 1 for the Rate of positive SARS-
Figure 1. Rate of positive SARS-CoV-2 PCR tests in the city of Bney Brak and in Israel following mass gathering events on Jewish New Year, September 18–
October 1st.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY 1327
CoV-2 PCR tests in the city of Bney Brak and in Israel following
mass gathering events on Jewish New Year, September 18–
October 1st.)
There were no reports of side effects and most users com­
mented on the ease of use and had no problem in adapting
the use of Taffix to their daily routine.
5. Discussion
This study shows a significant reduction in infection rate
among people who used Taffix for primary prevention of
SARS-CoV-2 infection, despite high-risk exposure and reduc­
tion of above 4 fold in the risk of infection. Primary prevention
in the context of a viral epidemic refers to the ability to
prevent persons from being infected. In general, primary pre­
vention can be achieved through measures such as altering
risky behavior, vaccination, pharmacotherapy, and other
measures.
During most of the COVID 19 pandemic health care orga­
nizations and authorities, for lack of a better alternatives, had
to refer to centuries-old measures such as social distancing
(the equivalent of the medieval ‘quarantine’ [7], the use of
masks by the general public [8] and hygiene. During the
last year unparalleled efforts were made to develop vaccines –
perhaps the only true primary prevention therapeutic modal­
ity using modern day technology. A look at the list of drugs
approved by Emergency Use Authorization by FDA indicates
that with the exception of vaccine all approved drugs,
whether antivirals, anti neoplastic or immune modulating,
were aimed at the complications of COVID-19 disease in mod­
erate to severe disease [9]. Most of the scientific work was
focused on ameliorating disease severity and reducing mor­
tality. Very few primary prevention measures were suggested
1328 K. SHMUEL ET AL.
and evaluated such as vitamin D, Hydroxy Chloroquine and
diet.
The role of Vit D in primary prevention of COVID-19 and in
ameliorating disease severity and mortality is still not clear:
Vitamin D may enhance innate and adaptive immunity.
Because antigen-presenting cells have the ability to synthesize
1,25-dihydroxyvitamin D from 25-hydroxyvitamin D, it has
been postulated that vitamin D3 supplementation could
improve the function of macrophages and dendritic cells,
thereby ameliorating overall immune response. Illie et al
reported negative correlations between mean levels of vita­
min D in each country and the number of COVID-19 cases/1 M,
and mortality. Vitamin D levels were severely low in the aging
population especially in Spain, Italy and Switzerland. This is
also the most vulnerable group of the population in relation to
COVID-19 [10]. Mordaca reviewed Vitamin D ‘s many mechan­
isms by which it reduces the risk of microbial infection and
death, including physical barrier, cellular natural immunity,
and adaptive immunity. Vitamin D supplementation has
shown favorable effects in viral infections including influenza
and HIV. However he concluded that the effects of vitamin
D supplementation during COVID-19 infection sill remain con­
troversial [11]. On 17 December 2020, the National Institute for
Health and Care Excellence (NICE), in collaboration with Public
Health England and the Scientific Advisory Committee on
Nutrition, published an updated rapid review of recent studies
on vitamin D and COVID-19. Their recommendations support
the current government advice, revised in April, 2020, during
the first lockdown in the UK, for everyone to take vitamin
D supplements to maintain bone and muscle health during
the autumn and winter months however as for prevention of
COVID-19 infection the panel concluded that there is insuffi­
cient evidence to support this claim at this time [12].
The role of Hydroxychloroquine (HCQ) and chloroquine
(CQ) during the COVID-19 epidemic was rightly termed: ‘The
never ending story.’ [13]. The antiviral effects of CQ and HCQ
have been demonstrated in vitro due to their ability to block
viruses like coronavirus SARS in cell culture. CQ and HCQ have
been proposed to reduce immune reactions to infectious
agents, inhibit pneumonia exacerbation, and improve lung
imaging investigations. CQ analogs have also revealed the
anti-inflammatory and immunomodulatory effects in treating
viral infections and related ailments. . Hydroxychloroquine was
advocated as an effective primary prevention pharmacother­
apy: In a recently published systematic review and meta-
analysis Lewis et al [14] looked at the evidence for primary
prevention of COVID-19 with HCQ among health care workers.
and concluded that although pharmacologic prophylaxis is an
attractive preventive strategy against COVID-19, the current
body of evidence failed to show clinical benefit for prophylac­
tic hydroxychloroquine and showed a higher risk of adverse
events when compared to placebo or no prophylaxis.
Microbiome’s influence on human health is attracting the
interests of scientists and the public alike. In the context of
COVID-19, the higher risk of disease severity and mortality
associated with Obesity, Diabetes and pregnancy serves as
another indirect indicator that microbiome differences asso­
ciated with genetic, ethnic and cultural background could
explain some of the additional risk associated with COVID-19
in certain patients groups [15] . These facts makes it critical to
consider both how the microbiome, shaped by biosocial pro­
cesses, affects susceptibility to the coronavirus and, conver­
sely, how COVID-19 disease and prevention measures may
affect the microbiome. This knowledge may prove key in
prevention and treatment, and long-term biological and social
outcomes of this pandemic. This issue remained open as
additional studies are required to deepen our understanding
on this potentially important topic [16].
On this background, the approach of primary prevention in
the nasal cavity suggested here by Taffix is novel and may
have significant implications on public health:
We conducted a prospective user survey in a densely popu­
lated city, during peak epidemic period with high incidence of
transmission ahead of what was perceived to be a super-
spreading event during the Jewish Rosh Hashana prayers.
Based on prior in vitro studies conducted by the developers
that showed high viricidal activity of the Taffix against SARS-
CoV-2 (6) the prospective users survey was performed to
gauge the real life effect of Taffix in preventing further out­
break of COVID-19 disease before an event that involved mass
gathering of people. Users reported a substantially lower
infection rates compared with persons from the same com­
munity with similar exposure. This significant reduction
despite high risk exposure suggests significant effectiveness
of Taffix in prevention of SARS-CoV-2 infection and reduction
of above 4-fold in the risk of infection. Of note in this time
period the number of new cases in the city of Bney Brak
increased by 1.6 folds as positivity rates went from 17.6%
to 28.4.
Comparison of the demographics between the users and
non users need some explanation:
The ratio of females to males among the users group (35%-
65%) is probably influenced by the fact that Taffix is not
recommended for use in pregnant and breast feeding
women without prior consultation with their physician. The
average birth rate in Israel orthodox community is 6.6 children
per woman, in comparison to 2.7 in non-orthodox population
[17]- and could explain the under representation of females in
the user’s group. The under representation of female among
the user’s group should actually strengthen the finding of our
study since women in the city of Bney Brak were found to
have a significantly less prone to contracting COVID:19
A serological survey in Beney Beraq – A Joint Project of the
CBS, Israel Ministry of Health, Gertner Institute and Bney Beraq
Municipality [18] found a significant difference between males
and females positive serological testing for SARS-CoV-2: 12.1%
vs 6,2%. This survey included some 20000 participants repre­
sentative of the total inhabitants of the city. Serological results
were found to be highly correlated to prior SARS-CoV-2 PCR
testing . One would expect higher risk of infection among
a group were males are over represented – this was not the
case in our survey.
Another age group that was precluded from being properly
represented in the user group was the age group below
18 years of age – while among the non-users children below
age 18 comprise some 47% - (similar to the general demo­
graphics in the city of Bney Brak 48% [19]) of the group – only
33.6% of the users were below 18 since Taffix is not

recommended for children below the age of 12. There are
several limitation of the study that should be discussed: Our
results could be influenced by selection bias whereby people
who were more concerned about the possibility of infection
would choose to use any additional protection offered to
them and might be more careful in observing social distancing
and use of masks.
While this certainly is a possibility several points should be
considered: 1. Prayers in the synagogue were performed in
compaince with safety measures such as masks and social
distancing. (see methods). 2. Even in countries where the use
of masks and social distancing was adhered to and enforced-
the infection rate dropped dramatically but did not reach
anything near zero infection rate – attesting the relative but
not absolute protection of these measures [20]. 3. On
a community level even reducing infection rate among people
who are more aware of the risks and are not fully protected
due to the limitation of the current safety measures and
extremely high prevalence in the community- can significantly
lower the numbers of patients and the risks associated with
contracting the disease. 4. These results suggest further that
Taffix provided protection to people who used it as instructed,
not only in the community gathering but also at home, where
they did not wear a mask, even when they had an infected
family member leaving in the same household.
Additional limitation of this user survey might be the rela­
tively small size of the community and the under-
representation of women of childbearing age and teen agers
in the users group compared to the non-users explained
above. As such conclusion with regards to these age groups
should be considered more carefully. Obviously, a prospective
clinical study will enrich our understanding of the relative
efficacy and the specific circumstances where Taffix will be
most efficient in preventing infection. That being said the
results of this user survey indicate that among users of Taffix
there was a significantly lower infection rate with SARS-CoV-2
infection.
6. Conclusion
Our prospective user survey showed lower SARS-CoV-2 infec­
tion rates in Taffix users during a high risk mass gathering. No
adverse events were reported. Further evaluation by con­
trolled clinical trials will be helpful in defining more precisely
target populations and means of encouraging adherence.
To our knowledge this is the first time that any measure to
prevent infection in SARS-CoV-2 virus was proven effective
beyond the use of masks. Until such time that global vaccina­
tion will be achieved – strengthening the current safety
measure could be meaningful in curbing the spread of infec­
tion. Given the excellent safety profile of Taffix and its sig­
nificant efficacy in preventing infection following what is
defined as high-risk infection event – it seems that this addi­
tional layer of protection may have a role in reducing the
risks of infection. . While our results are based on real life
survey – the significant difference between users and non
users of an additional layer of protection is noteworthy. While
world wide, countries are struggling to reach high level of
immunity through vaccination, and current safety measures
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY 1329
such as social distancing and use of masks have proven
insufficient, these finding could indeed raise some hope
and be added to our meager arsenal for preventing the SARS-
CoV-2 infection.
Funding
Nasus Pharma is the manufacturer of Taffix and has donated the product
for the survey and paid for statistical and data analysis performed by
independent company (Medistat).
Declaration of interest
D Megiddo is the CEO of Nasus Pharma, the manufacturer of Taffix.
T Lapidot is the VP clinical of Nasus Pharma, the manufacturer of Taffix.
The authors have no other relevant affiliations or financial involvement
with any organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the manuscript
apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have received an honorarium for their
review work, Peer reviewers on this manuscript have no other relevant
financial or other relationships to disclose.
Author contributions
SK and YN developed the study protocol and participated in the analysis
of the results and the written manuscript
DM and TL developed the study protocol and participated in the
analysis of the results and the written manuscript as well as in the follow
up and operation of the study
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